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. 2020 Jul;11(3):338-347.
doi: 10.1177/1947603518789997. Epub 2018 Aug 6.

Modeling and Staging of Osteoarthritis Progression Using Serial CT Imaging and Arthroscopy

Candace Flynn  1 , Mark Hurtig  1 , Emma Lamoure  1 , Erin Cummins  1 , Valeria Roati  1 , Mark Lowerison  2 , Sang Young Jeong  3 , Wonil Oh  3 , Alex Zur Linden  1
Affiliations

Modeling and Staging of Osteoarthritis Progression Using Serial CT Imaging and Arthroscopy

Candace Flynn et al. Cartilage. 2020 Jul.

Abstract

Objective: The objective of this study was to describe in life methods by which osteoarthritis can be staged in order to time therapeutic interventions that are relevant to osteoarthritis (OA) clinical trials.

Methods: Twenty-two sheep underwent arthroscopic meniscal destabilization to induce OA. Serial computed tomography (CT) imaging and arthroscopy were used to monitor osteoarthritis progression at 3-month intervals over 9 months. Eleven sheep received 1 intra-articular injection of hyaluronate 3 months after OA induction and another group of 11 received saline. A linear mixed model was used to define the trajectory of shape change in the medial joint compartment. Ordinal logistic regression was used to investigate the association between morphological changes and sclerosis.

Results: Three months after meniscal destabilization there were early bipolar chondral lesions in the medial compartment of the knee, as well as osteophytes and bone remodeling. Superficial fissures and cartilage cracks progressed to discrete areas of cartilage thinning and fibrillation on the medial tibial plateau by 6 months that became cartilage erosions by nine months. A linear mixed effect model demonstrated significant change in medial compartment length and width with over time (P < 0.05) for both groups. A significant association between severity of sclerosis and medial compartment morphology was also observed.

Conclusions: The induction of osteoarthritic lesions with meniscal release model can be followed using noninvasive and minimally invasive procedures allowing for real-time decisions about redosing therapies, or other changes such as extending trial timelines without sacrificing animals to conduct assessments.

Keywords: animal model; intervention; osteoarthritis; trajectory.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
An arthroscopic view of the normal anterior aspect of the medial femorotibial joint. The dashed line indicates the locations for transection transection of the anterior meniscotibial ligament (vertical) and meniscal capsular attachment (horizontal incision).
Figure 2.
Figure 2.
Measurements of width and length (mm) of medial femoral condyle (MFC) and medial tibial plateau (MTP) of the right knee joint using the LineTool in OSiriX required consistent positioning. The 3-dimensional image was rotated in the coronal and transverse planes through both collateral ligament attachment sites resulting in the widest possible the joint space. The MTP width was measured from this specific projection. Similarly, the MFC and MTP length were measured using sagittal projections that maximized joint width and superimposed medial and lateral condyles exactly. (A) Width of the MFC (cm). (B) Width of the MTP (cm). (C) Length of the MFC (cm) and (D) length of the MTP (cm).
Figure 3.
Figure 3.
Sclerosis was graded from 0 (normal) to 4 (severed) based on increasing gray scale brightness and the area of subchondral plate affected. (A) Grade 1, (B) grade 2, (C) grade 3, and (D) grade 4.
Figure 4.
Figure 4.
Mean and standard deviation of sheep in group 1 that received intra-articular saline and group 2 that received intra-articular hyaluronate at week 12. Between postoperative week 3 and 19, there was no observed lameness, lameness peaked between 25 and 29 weeks after meniscal release. There were no significant differences between the two groups at any time point.
Figure 5.
Figure 5.
Example of medial joint surface enlargement. Measurement of medial femoral condyle (MFC) width for 1 subject taken at month 0 and month 9 using OSiriX 3-dimensional rendering platform and linear measurement tool. (A) Width of MFC taken at week 0 (preoperative). (B) Width taken at week 35, or 9 months postmeniscal release. (C) Coronal view of MFC at week 0. (D) Coronal view of MFC and medial tibial plateau (MTP) taken at week 35. Arrow denotes area of bone remodeling and widening of the MFC.
Figure 6.
Figure 6.
Trajectory of relative change in length of the medial tibial plateau (MTP) since Week 0 (preoperative) with regard to time is described for saline and hyaluronate condition. Average relative change was determined at weeks 9, 24, and 35.
Figure 7.
Figure 7.
Trajectory of relative change in width of the medial tibial plateau (MTP) since week 0 (preoperative) with regard to time is described for saline and hyaluronate condition. Average relative change was determined at weeks 9, 24, and 35.
Figure 8.
Figure 8.
Trajectory of relative change in length of the medial femoral condyle (MFC) with regard to time for saline and hyaluronate treatment groups. Average relative change was determined at weeks 9, 24, and 35.
Figure 9.
Figure 9.
Trajectory of relative change in width of the medial femoral condyle (MFC) with regard to time is described for saline and hyaluronate treatment groups. Average relative change was determined at weeks 9, 24, and 35.
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